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R. H. MOLE 



tumour development with different body burdens should be proportional to 

 the square of the body burden as they seem in fact to be. 



When a single injection of any radioactive material is given there is a 

 progressive fall in the amount retained so that the number of radioactive 

 disintegrations per unit of time is variable not constant. When allowance is 

 made for this progressive reduction in body burden with time, the data from 



(£+25 -ev 



Fig. 3. Age-specific incidence rate of bone tumours in mice given montlily injections of ^®Sr 

 (data of Brues, 1949). Tiie bone-tumour rates are plotted against the square of the number of 

 radioactive disintegrations in a manner detailed by Mole (1962). The straight lines are drawn 

 by eye through the origin so that their slopes shall be proportional to the squares of the 

 monthly doses (shown in /xc/kg against each line). 



an experiment of Finkel and her colleagues utihzing a single injection of ^°Sr 

 also seem to fit the prediction that the rate of tumour development with 

 different body burdens should be proportional to the square of the nmnber of 

 preceding radioactive events (Fig. 4). 



Unfortunately without knowing more about the exact site in bone where 

 the carcinogenic change begins it is not possible to utilize the hypothesis to 

 compare the carcinogenic potency of radioactive materials of different 

 physical chemical and metabolic properties. It is also the case that the 

 hypothesis has not yet been checked against a number of important experi- 

 ments in which the method of administration of the radioactive isotope has 

 been varied as by fractionation of injections or by continuous feeding in the 

 diet (Finkel et al., 1960a, b). The full results of these experiments have not yet 

 been reported. Nevertheless one general conclusion may be drawn. If it is 

 true that overt cancer begms only after the conjunction of two rare events then 

 in a group of animals with just 100% incidence of tumours this conjunction 



